RGD Reference Report - Genetic polymorphisms in the methylenetetrahydrofolate reductase and thymidylate synthase genes and risk of hepatocellular carcinoma. - Rat Genome Database

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Genetic polymorphisms in the methylenetetrahydrofolate reductase and thymidylate synthase genes and risk of hepatocellular carcinoma.

Authors: Yuan, Jian-Min  Lu, Shelly C  Van Den Berg, David  Govindarajan, Sugantha  Zhang, Zhen-Quan  Mato, Jose M  Yu, Mimi C 
Citation: Yuan JM, etal., Hepatology. 2007 Sep;46(3):749-58. doi: 10.1002/hep.21735.
RGD ID: 14696708
Pubmed: PMID:17659576   (View Abstract at PubMed)
PMCID: PMC2391240   (View Article at PubMed Central)
DOI: DOI:10.1002/hep.21735   (Journal Full-text)


UNLABELLED: Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS) are known to play a role in DNA methylation, synthesis, and repair. The genetic mutations in MTHFR and TYMS genes may have influences on their respective enzyme activities. Data on the association studies of the MTHFR and TYMS genetic polymorphisms and risk of hepatocellular carcinoma (HCC) are sparse. MTHFR and TYMS genotypes were determined on 365 HCC cases and 457 healthy control subjects among Hispanic and non-Hispanic whites and African-Americans in Los Angeles County, California, and among Chinese in the city of Nanning, Guangxi, China. Relative to the high-activity genotype, each low-activity genotype of MTHFR was associated with a statistically nonsignificant 30% to 50% reduction in risk of HCC. Relative to the TYMS3'UTR +6/+6 genotype, individuals with 1 or 2 copies of the deletion allele had a statistically significant 50% reduction in risk of HCC. When we examined HCC risk by the total number of mutant alleles in the 3 polymorphic loci of MTHFR/TYMS (range, 0-4), there was a monotonic decrease in risk with increasing number of mutant alleles (P for trend = 0.003). Individuals possessing the maximum number of mutant alleles (i.e., 4) had an odds ratio of 0.46 (95% confidence interval = 0.23-0.93) for HCC compared with those with no or only 1 mutant allele.
CONCLUSION: This study supports the hypothesis that reduced MTHFR activity and enhanced TYMS activity, both of which are essential elements in minimizing uracil misincorporation into DNA, may protect against the development of HCC.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hepatocellular carcinoma susceptibilityIAGP 14696708DNA:SNPs: :677C>T and 1298A>C(human)RGD 
hepatocellular carcinoma susceptibilityISOMTHFR (Homo sapiens)14696708; 14696708DNA:SNPs: :677C>T and 1298A>C(human)RGD 
hepatocellular carcinoma susceptibilityIAGP 14696708DNA:deletion:3'UTR:1494del6(human)RGD 
hepatocellular carcinoma susceptibilityISOTYMS (Homo sapiens)14696708; 14696708DNA:deletion:3'UTR:1494del6(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mthfr  (methylenetetrahydrofolate reductase)
Tyms  (thymidylate synthetase)

Genes (Mus musculus)
Mthfr  (methylenetetrahydrofolate reductase)
Tyms  (thymidylate synthase)

Genes (Homo sapiens)
MTHFR  (methylenetetrahydrofolate reductase)
TYMS  (thymidylate synthetase)


Additional Information